Trisubstituted benzoic acid intermediates

ABSTRACT

Novel trisubstituted benzoic acid intermediates which are useful in the preparation of certain herbicidal 2-(2,3,4-trisubstituted benzoyl)-1,3-cyclohexanediones are described.

This is a divisional of application Ser. No. 07/273,391, filed Nov. 18, 1988, now abandoned.

BACKGROUND OF THE INVENTION

Certain 2-(2'3'4'tri-substituted benzoyl)--1,3-cyclohexanedione herbicides are described in U.S. Pat. No. 4,780,127, issued Oct. 25, 1988, U.S. application Ser. No. 129,026, filed Dec. 4, 1987; and a U.S. application entitled 2-(2',3',4'-trisubstituted benzoyl)--1,3-cyclohexanediones, with William J. Michaely, inventor, filed herewith, and all incorporated herein by reference.

The above-described herbicidal compounds can have the following structural formula ##STR1## wherein R⁷ through R¹² are hydrogen or C₁ -C₄ alkyl; R¹ is C₁ -C₄ alkyl, C₁ -C₄ haloalkyl, CH₂ CH₂ -OCH₃, CH₂ CH₂ OC₂ H₅, CH₂ CH₂ SCH₃, or CH₂ CH₂ SC₂ H₅ ; R² is C₁ -C₄ alkyl; and n is the integer 0 or 2.

These herbicides can be prepared by reacting a dione of the structural formula ##STR2## wherein R⁷ through R¹² are as defined with a mole of trisubstituted benzoyl chloride of the structural formula ##STR3## wherein n, R¹ and R² are as defined above.

DESCRIPTION OF THE INVENTION

This invention has several embodiments which are as follows:

Embodiment A relates to novel intermediate compounds having the structural formula ##STR4## wherein R is cyano; carboxy; or --CO₂ R_(a) where R_(a) is C₁ -C₄ alkyl, preferably ethyl; most preferably R is --CO₂ C₂ H₅.

Embodiment B relates to novel intermediate compounds having the structural formula ##STR5## wherein R is cyano; carboxy or --CO₂ R_(a) wherein R_(a) is C₁ -C₄ alkyl, preferably ethyl, most preferably R is --CO₂ C₂ H₅ and R¹ is C₁ -C₄ alkyl; preferably C₁ -C₂ alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅, with the proviso that when R is carboxy, then R¹ is --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.

Embodiment C relates to novel intermediate compounds having the structural formula ##STR6## wherein R is cyano; carboxy or --CO₂ R_(a) wherein R_(a) is C₁ -C₄ alkyl, preferably ethyl, most preferably R is CO₂ C₂ H₅ ; R¹ is C₁ -C₄ alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅ and R² is C₁ -C₄ alkyl, preferably methyl, ethyl or n-propyl with the proviso that when R is carboxy, then R¹ is --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.

Embodiment D relates to novel intermediate compounds having the structural formula ##STR7## wherein X is chlorine or hydroxy; R⁴ is --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅, preferably --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅ ; and R² is C₁ -C₄ alkyl, preferably methyl, ethyl or n-propyl.

Embodiment E relates to novel intermediate compounds having the structural formula ##STR8## wherein X is hydroxy or chlorine; R³ is --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅ and R² is C₁ -C₄ alkyl, preferably methyl, ethyl or n-propyl.

Embodiment F relates to novel intermediate compounds having the structural formula ##STR9## wherein R^(a) is C₁ -C₄ alkyl, preferably ethyl, R⁵ is C₁ -C₄ alkyl; C₁ -C₄ haloalkyl; --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅ ; preferably --CH₂ CH₂ OCH₃ or --CH₂ CH₂ OC₂ H₅ and R² is C₁ -C₄ alkyl, preferably methyl, ethyl or n-propyl.

In embodiments A-C, the group R can also be trifluoromethyl.

The several intermediate compounds of this invention can be prepared by the general method shown in the Figure of the next page with R, R¹, R² and R⁵ being as defined. The group R^(z) is C₁ -C₄ alkyl. ##STR10##

Referring to the Figure, and particularly to Reaction Steps (A) through (G), consider the following:

Generally in Reaction Step (A), a mole amount of the 3-substituted phenol is reacted with 2 moles of chlorine and a catalytic amount of a C₁ -C₁₀ alkylamine, preferably tert-butylamine or diisopropylamine in a solvent such as methylene chloride, at a temperature between -70° C. to 70° C. After this reaction, the free chlorinated phenol is isolated by normal procedures.

For Reaction Step (B), one mole of the dichloro-substituted phenol reaction product of Step (A) is reacted with an appropriate alkylating agent such as a 2-chloroethyl ethyl ether, 2-chloroethyl methyl ether, 2-chloroethyl methyl sulfide, 2-chloroethyl ethyl sulfide or C₁ -C₄ alkylchloride along with a catalytic amount of potassium iodide and a mole excess of a base such as potassium carbonate. Alkyl iodides such as methyl iodide or ethyl iodide may also be used. In these cases the catalytic potassium iodide is not needed and little or no heat is required. The reaction is run at 25° C. to 80° C. for 4 hours with agitation. The reaction product is recovered by conventional techniques.

For Reaction Step (C), the dichloro compound from Reaction Step (B) is reacted with an equal mole amount of a C₁ -C₄ alkyl mercaptan along with a mole excess of a base such as potassium carbonate in a solvent such as dimethylformamide. The reaction is run for several hours at a temperature between 50° C. to 100° C. with stirring under an inert atmosphere such as nitrogen. The desired reaction product is recovered by conventional techniques.

For Reaction Step (D) a mole amount of the alkyl ester of 2-chloro-4-alkylthio benzoic compound is oxidized with at least 3 moles of an oxidizing agent such as m-chloroperbenzoic acid in a suitable solvent such as methylene chloride by stirring a solution of the reactants at 20° to 100° C. The desired intermediate is recovered by conventional techniques. During this reaction step the 4-alkylthio substituent is oxidized to the corresponding alkylsulfone.

For Reaction Step (E) a mole amount of the 2-chloro-3-substituted-4-alkylthio ester or cyano compound is hydrolyzed with a base such as sodium hydroxide to the corresponding 2-chloro-3-substituted-4-alkylthio benzoic acid. The hydrolysis is run in a solvent such as an 80 percent methanol-water mixture. The reaction can be run at 25°-100° C. with stirring. The desired product is recovered by conventional techniques.

For Reaction Step (F) the alkyl ester of the trisubstituted benzoic acid is converted to the trisubstituted benzoic acid by the hydrolysis step taught in Reaction Step (E).

In the alternative, the tri-substituted benzoic acid reaction product of Reaction Step (F) can be directly prepared from the reaction product of Reaction Step (C) by a combination hydrolysis of the 2-chloro-3-substituted-4-alkylthio ester or cyano compound to the corresponding benzoic acid and an oxidation of the 4-alkylthio substituent to the corresponding 4-alkylsulfone. The hydrolysis and oxidation steps can be jointly carried out by reacting a mole of the ester or cyano compound with at least 5 moles of sodium or calcium hypochlorite in a suitable solvent such as dioxane-water, by heating a solution of the reactants from about 25° C. to about 100° C., followed by the acidification with concentrated hydrochloric acid. Filtration of the resulting precipitate yields the desired product.

For Reaction Step (G) the dichloro compound from Reaction Step (B) is converted to the benzoic acid by the hydrolysis step taught in Reaction Step (E).

The intermediate benzoic acids described herein can easily be converted to their respective acid chlorides and then to their acid cyanides, if desired, by the following two reactions. First, a mole of oxalyl chloride and a catalytic amount of dimethylformamide in a suitable solvent such as methylene chloride at a temperature of 20° to 40° C. for 1 to 4 hours is heated with a mole of the intermediate benzoic acid. The corresponding benzoic acid cyanide can easily be prepared from the benzoic acid chloride by reaction with cuprous cyanide at a temperature of 50° to 220° C. for 1 to 2 hours.

The trisubstituted benzoic acid chloride intermediates are useful in the preparation of the previously described herbicidal 2-(2',3',4'-trisubstituted benzoyl)--1,3-cyclohexanediones.

The following series of examples teach the synthesis of representative intermediate compounds of this invention. The structures of all compounds of the examples and tables were verified by nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and mass spectroscopy (MS).

EXAMPLE 1 Ethyl 2,4-chloro-3-hydroxybenzoate ##STR11##

In a 3-neck, 1-liter flask equipped with a mechanical stirrer, condenser, thermometer and a diffusion tube was added a solution of 106 grams (0.64 mole) ethyl 3-hydroxybenzoate and 0.5 grams diisopropylamine in 600 milliliters (ml) dichloroethane at reflux. Chlorine (112 grams, 1.6 mole) was added through the diffusion tube over a period of 6 hours then let cool to room temperature. After cooling, the solution was washed with 200 ml 5% sodium bisulfite solution, then with 200 ml water, dried (MgSO₄) and reduced under vacuum. Yield was 151 g of an oil. This mixture of chlorinated compounds (66% above product) can be recrystallized in ether/pentane by cooling to -20° C. to give pure ethyl 2,4-dichloro-3-hydroxybenzoate. The structure of this compound and all examples were verified by nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and mass spectroscopy (MS).

Additional compounds were prepared by the same procedure as described in Example 1 and are listed in Table 1.

                  TABLE 1     ______________________________________      ##STR12##     R               Yield (%) m.p. °C.     ______________________________________     CO.sub.2 CH.sub.3                     72        57-64     CO.sub.2 CH(CH.sub.3).sub.2                     66        oil     ______________________________________

EXAMPLE 2 Ethyl 2,4-chloro-3-(2-methoxyethoxy) benzoate ##STR13##

A solution of 18 g (77 millimoles, mmol) ethyl 2,4-dichloro-3-hydroxybenzoate, 22 g (3 equivalents) (eq) 2-chloroethyl methyl ether, 22 g (2 eq) potassium carbonate and ca. 0.5 g sodium iodide in 100 ml DMF was heated at 80° C. for 1.5 hours. To the cooled solution was added 400 ml ether. The organic phase was washed with 100 ml water (2 times), 100 ml 100% NaOH and 100 ml 10% HCl. Dried (MgSO₄) and reduced under vacuum. The yield was 20 g (68 mmole).

Additional compounds were prepared by the same procedure as described in Example 2 (except in those cases using alkyl iodide then the potassium iodide catalyst was omitted and little or no heat is required) and are listed in Table 2.

                  TABLE 2     ______________________________________      ##STR14##                             Physical     R         R.sup.1       Property Yield (%)     ______________________________________     CO.sub.2 C.sub.2 H.sub.5               C.sub.2 H.sub.5                             oil      92     CO.sub.2 C.sub.2 H.sub.5               n-C.sub.3 H.sub.7                             oil      100     CO.sub.2 C.sub.2 H.sub.5               CH.sub.2 CH.sub.2 OCH.sub.3                             oil      30     CO.sub.2 C.sub.2 H.sub.5               CH.sub.2 CH.sub.2 Br                             oil      95     CO.sub.2 C.sub.2 H.sub.5               CH.sub.2 CH.sub.2 SCH.sub.2 H.sub.5                             oil      66     CO.sub.2 C.sub.2 H.sub.5               CH.sub.2 CH.sub.2 Cl                             oil      10     CO.sub.2 CH.sub.3               CH.sub.2 CF.sub.3                             solid    57     ______________________________________

EXAMPLE 3 Ethyl 2-chloro-3-(2-methoxyethoxy)-4-ethylthiobenzoate ##STR15##

A solution of 10 g (34 mmole) ethyl 2,4-dichloro-3-(2-methoxyethoxy)benzoate, 10 g (4 eq) ethanethiol and 10 g (2 eq) potassium carbonate in 100 ml DMF was heated (approximately 100° C.) for 2 hours, then let cool overnight. Added 400 ml diethyl ether and washed with 100 ml water (two times), 100 ml 10% HCl and 100 ml 10% NaOH. Dried (MgSO₄) and reduced under vacuum. Yield 10 g (31 mmole) of an oil.

Additional compounds were prepared by the same procedure as described in Example 3 and are listed in Table 3.

                  TABLE 3     ______________________________________      ##STR16##     R         R.sup.1       R.sup.2 Yield (%)     ______________________________________     CO.sub.2 C.sub.2 H.sub.5               C.sub.2 H.sub.5                             C.sub.2 H.sub.5                                     64     CO.sub.2 C.sub.2 H.sub.5               n-C.sub.3 H.sub.7                             CH.sub.3                                     41     CO.sub.2 C.sub.2 H.sub.5               CH.sub.2 CH.sub.2 OCH.sub.3                             C.sub.2 H.sub.5                                     46     CO.sub.2 C.sub.2 H.sub.5               CH.sub.2 CH.sub.2 OCH.sub.3                             n-C.sub.3 H.sub.7                                     86     CO.sub.2 C.sub.2 H.sub.5               H             C.sub.2 H.sub.5                                     15     CO.sub.2 CH.sub.3               H             C.sub.2 H.sub.5                                     --     CO.sub.2 CH.sub.3               CH.sub.2 CH.sub.2 OCH.sub.3                             C.sub.2 H.sub.5                                     90     CO.sub.2 CH.sub.3               CH.sub.2 CH.sub.2 OCH.sub.3                             n-C.sub.3 H.sub.7                                     87     CO.sub.2 CH.sub.3               CH.sub.2 CH.sub.2 OCH.sub.3                             CH.sub.3                                     65     CO.sub.2 CH.sub.3               CH.sub.2 CF.sub.3                             C.sub.2 H.sub.5                                     53     ______________________________________

EXAMPLE 4 Ethyl 2-chloro-3-(2-methoxyethoxy)-4-ethylsulfonyl benzoate ##STR17##

The ester, ethyl 2-chloro-3-(2-methoxyethoxy)-4-ethylthiobenzoate from Example 3 (10 g) was dissolved in 100 ml of methylene chloride and cooled with an ice bath. Next 18 g solid m-chloroperoxybenzoic acid (85% pure, 2.2 equivalents) was added in portions over a period of 2 hours. The crude reaction mixture was allowed to warm to room temperature. After 1 hour at room temperature the excess peracid was destroyed with sodium bisulfite (100 ml 5% solution). The organic layer was washed two times with 5% sodium hydroxide (100%) and stripped under vacuum to give 11.3 grams of pure ethyl 2-chloro-3-(2-methoxyethoxy)-4-ethylsulfonylbenzoate as a viscous oil.

Additional compounds were prepared by the same procedure as described in Example 4 and are listed in Table 4.

                  TABLE 4     ______________________________________      ##STR18##     R.sup.a  R.sup.5       R.sup.2 Yield (%)     ______________________________________     C.sub.2 H.sub.5              C.sub.2 H.sub.5                            C.sub.2 H.sub.5                                    90     C.sub.2 H.sub.5               -n-C.sub.3 H.sub.7                            CH.sub.3                                    64     C.sub.2 H.sub.5              C.sub.2 H.sub.4 OCH.sub.3                            C.sub.2 H.sub.5                                    72     C.sub.2 H.sub.5              C.sub.2 H.sub.4 OCH.sub.3                            n-C.sub.3 H.sub.7                                    98     CH.sub.3 CH.sub.2 CH.sub.2 Cl                            n-C.sub.3 H.sub.7                                    --     CH.sub.3 C.sub.2 H.sub.4 OCH.sub.3                            C.sub.2 H.sub.5                                    100     CH.sub.3 C.sub.2 H.sub.4 OCH.sub.3                            n-C.sub.3 H.sub.7                                    97     CH.sub.3 CH.sub.2 CH.sub.2 OCH.sub.3                            CH.sub.3                                    87     CH.sub.3 CH.sub.2 CF.sub.3                            CH.sub.3                                    --     ______________________________________

EXAMPLE 5 2-chloro-3-(2-methoxyethoxy)-4-ethylsulfonylbenzoic acid ##STR19##

To 11.3 g (0.03 mole) of the ethyl 2-chloro-3-(2-methoxyethoxy)-4-ethylsulfonylbenzoate in 100 ml of 96% ethanol was added dropwise 16 ml (1.2 eq) of 10% sodium hydroxide. After stirring at room temperature for 4 hours, 100 ml of diethyl ether was added and the organic phase was extracted with 50 ml of 5% NaOH. The aqueous phase was acidified with 10% HCl and extracted two times with 50 ml chloroform. The organic phase was dried with MgSO4 and concentrated under vacuum to yield 8.8 grams of 2-chloro-3-(2-methoxyethoxy)4-ethylsulfonylbenzoic acid as a viscous oil.

Additional compounds were prepared by the same procedure as described in Example 5 and are listed in Table 5.

                  TABLE 5     ______________________________________      ##STR20##     R.sup.5         R.sup.2 Yield (%)     ______________________________________     CH.sub.2 CH.sub.2 OCH.sub.3                     n-C.sub.3 H.sub.7                             77     CH.sub.2 CH.sub.2 OCH.sub.3                     CH.sub.3                             80     ______________________________________

EXAMPLE 6 2-Chloro-3-(2-methoxyethoxy)-4-ethylthio benzoic acid ##STR21##

Three grams (8.2 mmol) ethyl 2-chloro-3-(2-methoxyethoxy)-4-propanethiobenzoate was dissolved in 20 ml 96% ethyl alcohol. To this was added 3.9 ml 10% sodium hydroxide in water. After stirring 4 hours at room temperature, 100 ml of diethyl ether was added to the solution. The solution was extracted twice with 50 ml 5% sodium hydroxide solution. The combined caustic extracts were acidified with 10% hydrochloric acid and extracted twice with 50 ml portions of chloroform. The chloroform extracts were dried over magnesium sulfate and the chloroform removed in vacuo to afford the free acid (2.0 g, 72%) as a soft solid.

Additional compounds were prepared by the same procedure as described in Example 6 and are listed in Table 6.

                  TABLE 6     ______________________________________      ##STR22##     R.sup.1          R.sup.2                             Yield (%)     ______________________________________     CH.sub.2 CH.sub.2 OCH.sub.3                      C.sub.2 H.sub.5                             72     ______________________________________

EXAMPLE 7 2,4-Dichloro-3-(2-methoxyethoxy) benzoic acid ##STR23##

Sixteen grams (41 mmol) ethyl 2,4-dichloro-3-(2-methoxyethoxy)benzoate was dissolved in 100 ml of 96% ethanol. To this was added, in portions, 18 ml (ca 1.1 equivalents) 10% sodium hydroxide. After stirring 4 hours at room temperature, 250 ml diethyl ether was added to the solution. The solution was extracted twice with 50 ml 5% sodium hydroxide. The combined caustic extracts were acidified with a 10% hydrochloric acid solution and extracted twice with 75 ml portions of chloroform. The chloroform extracts were dried (magnesium sulfate) and the chloroform removed in vacuo to afford the free acid (12.8 g, 79%) as a white solid.

Additional compounds were prepared by the same procedure as described in Example 7 and are listed in Table 7.

                  TABLE 7     ______________________________________      ##STR24##     R.sup.1        Yield (%)     ______________________________________     CH.sub.2 CH.sub.2 SC.sub.2 H.sub.5                    100     ______________________________________

The above-described benzoic acids can be readily converted to their acid chlorides using oxalyl chloride and a catalytic amount of dimethylformamide. These acid chlorides can be reacted with the above-described 1,3-cyclohexanedione to prepare the above-described herbicidal 2,3,4-trisubstituted benzoyl-1,3-cyclohexanediones according to the following two-step reaction:

The process proceeds via the production of an enol ester intermediate as shown in reaction (1). The final product is obtained by rearrangement of the enol ester as shown in reaction (2). The two reactions may be conducted as separate steps by isolation and recovery of the enol ester using conventional techniques prior to conducting step (2), or by addition of a cyanide source to the reaction medium after the formation of the enol ester, or in one step by inclusion of the cyanide source at the start of reaction (1). ##STR25## wherein n and R¹, R² and R⁷ through R¹² are as defined above and the moderate base is such as tri-C₁ -C₆ alkylamine, pyridine, alkali metal carbonate or alkali metal phosphate.

Generally, in step (1) mole amounts of the dione and substituted benzoyl chloride are used, along with a slight mole excess of a moderate base. The two reactants are combined in an organic solvent such as acetonitrile, methylene chloride, toluene, ethyl acetate or dimethylformamide. The base and benzoyl reactant preferably are added to the reaction mixture with cooling. The mixture is stirred at 0° C.-50° C. reaction is substantially complete.

The reaction product is worked up by conventional techniques. ##STR26## wherein R¹, R² and R⁷ through R¹² are as defined above.

Generally, in step (2) a mole of the enol ester intermediate is reacted with 1 to 4 moles of the base, preferably about 2 moles of moderate base and from 0.01 mole to about 0.5 mole or higher, preferably around 0.1 mole of the cyanide source (e.g., potassium cyanide or acetone cyanohydrin). The mixture is stirred in a reaction pot until the rearrangement is substantially complete at a temperature below 80° C., preferably about 20° C. to about 40° C., and the desired product is recovered by conventional techniques.

The term "cyanide source" refers to a substance or substances which under the rearrangement conditions consists of or generates hydrogen cyanide and/or cyanide anion.

The process is conducted in the presence of a catalytic amount of a source of cyanide anion and/or hydrogen cyanide, together with a molar excess, with respect to the enol ester, of a moderate base.

Preferred cyanide sources are alkali metal cyanides such as sodium and potassium cyanide; cyanohydrins of methyl alkyl ketones having from 1-4 carbon atoms in the alkyl groups, such as acetone or methyl isobutyl ketone cyanohydrins; cyanohydrins of benzaldehyde or of C₂ -C₅ aliphatic aldehydes such as acetaldehyde, propionaldehyde, etc., cyanohydrins; zinc cyanide; and hydrogen cyanide itself. Hydrogen cyanide is considered most advantageous as it produces relatively rapid reaction and is inexpensive. Among cyanohydrins the preferred cyanide source is acetone cyanohydrin.

The cyanide source is used in an amount up to about 50 mole % based on the enol ester. It may be used in as little as about 1 mole % to produce an acceptable rate of reaction at about 40° C. on a small scale. Larger scale reactions give more reproducible results with slightly higher catalyst levels of about 2 mole %. Generally about 1-10 mole % of the cyanide source is preferred.

The process is conducted with a molar excess, with respect to the enol ester, of a moderate base. By the term "moderate base" is meant a substance which acts as a base yet whose strenght or activity as a base lies between that of strong bases such as hydroxides (which could cause hydrolysis of the enol ester) and that of weak bases such as bicarbonates (which would not function effectively). Moderate bases suitable for use in this embodiment include both organic bases such as tertiary amines and inorganic bases such as alkali metal carbonates and phosphates. Suitable tertiary amines include trialkylamines such as triethylamine, trialkanolamines such as triethanolamine, and pyridine. Suitable inorganic bases include potassium carbonate and trisodium phosphate.

The base is used in an amount of from about 1 to about 4 moles per mole of enol ester, preferably about 2 moles per mole.

When the cyanide source is an alkali metal cyanide, particularly potassium cyanide, a phase transfer catalyst may be included in the reaction. Particularly suitable phase transfer catalysts are the Crown ethers.

A number of different solvents may be usable in this process, depending on the nature of the acid chloride or the acylated product. A preferred solvent for this reaction is 1,2-dichloroethane. Other solvents which may be employed depending on the reactants or products include toluene, acetonitrile, methylene chloride, ethyl acetate, dimethylformamide, and methyl isobutyl ketone (MIBK).

In general, depending on the nature of the reactants and the cyanide source, the rearrangement may be conducted at temperatures up to about 50° C. 

What is claimed is:
 1. A compound having the structural formula ##STR27## wherein R is cyano, carboxy or CO₂ R_(a) wherein R_(a) is C₁ -C₄ alkyl and R₁ is --CH₂ CH₂ OCH₃, --CH₂ CH₂ OC₂ H₅, --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.
 2. A compound having the structural formula ##STR28##
 3. A compound having the structural formula ##STR29##
 4. A compound having the structural formula ##STR30## wherein R¹ is --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅.
 5. A compound having the structural formula ##STR31## wherein R^(a) is C₁ -C₄ alkyl and R¹ is --CH₂ CH₂ OCH₃ ; --CH₂ CH₂ OC₂ H₅ ; --CH₂ CH₂ SCH₃ or --CH₂ CH₂ SC₂ H₅. 